Liposomes are used extensively for targeting and delivery of anticancer drugs. However, this methodology frequently involves the passive release of the encapsulated drugs to the selected tissue sites. Matrix metalloproteinase-9 (MMP-9) is involved in the progression and metastasis of a large number of cancers. We demonstrate that MMP-9 mediated cleavage of substrate lipopeptides releases encapsulated contents from liposomes in the extracellular matrix of cancer cells.  When the liposomes are echogenic, the release of the liposomal contents is further enhanced by the application of diagnostic frequency ultrasound.  For release of liposomal contents in the cell cytosol, we have prepared polymer-coated, reduction sensitive, echogenic liposomes presenting the folate groups on the surface.  These liposomes are actively targeted to cervical cancer cells overexpressing the folate receptor and efficiently internalized.  The reducing environment of the cytosol rapidly releases the encapsulated anticancer drug from the liposomes, leading to cell death.

Contents release from echogenic liposomes with dual triggers

245th National Meeting (2013)

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